Many compounds, including those from natural sources such as plant-derived compounds, do not provide their full benefit when consumed by a subject because they are not sufficiently soluble, not readily taken up by cells, easily degraded/broken down in the digestive system, etc. In other words, they are less bioavailable than are other types of compounds. One example of compounds like these is Curcumin ((1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a hydrophobic polyphenol derived from the Curcuma longa rhizome. Curcumin has been identified as the active component of turmeric, which has been used for many years for its beneficial health properties. Over the past few years, researchers have confirmed that it has provides a variety of benefits such as antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticarcinogenic activities. Based upon various studies, curcumin has been suggested to have therapeutic potential for the treatment of diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. One group of authors has concluded that “[c]urcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA®, REMICADE®, and ENBREL®), a vascular endothelial cell growth factor blocker (e.g., AVASTIN®), human epidermal growth factor receptor blockers (e.g., ERBITUX®, ERLOTINIB®, and GEFTINIB®), and a HER2 blocker (e.g., HERCEPTIN®)” (Aggarwal, B. B. et al., Curcumin: the Indian solid gold. Adv Exp Med Biol. (2007) 595:1-75.).
In preclinical studies, curcumin has demonstrated the ability to inhibit tumor development in cell lines including, for example, oral epithelial, breast, gastric, hepatic, pancreatic, cervical, ovarian, and prostate. Some have proposed that curcumin be further developed as a cancer therapeutic because it induces apoptosis in cancer cells without inducing cytotoxic effects in healthy cells.
Curcumin is a bis-α,β-unsaturated β-diketone, being predominantly keto form in acidic and neutral solutions, and taking the more stable enol form in alkaline medium. It exhibits extremely low solubility in aqueous solution (2.99×10−8 M) and limited bioavailability. For example, Wahlstrom et al. demonstrated that oral administration of 1 g/kg of curcumin resulted in minimal levels of curcumin in blood plasma of rats, leading to the conclusion that curcumin is poorly absorbed from the gut (Wahlstrom, B; Blennow, G. A study on the fate of curcumin in the rat. Acta Pharmacol. Toxicol. (Copenhagen) 1978, 43 (2), 86-92). Various approaches to improve curcumin solubility have included, for example, encapsulation in polymeric micelles, polymeric nanoparticles, lipid-based nanoparticles, liposomes, and hydrogels.
The “benefits of curcumin . . . are curtailed by its low oral bioavailability. Therefore, improvement of curcumin's oral bioavailability should be addressed in functional food research” (Hailong Yu and Qingrong Huang, Investigation of the Absorption Mechanism of Solubilized Curcumin Using Caco-2 Cell Monolayers, J. Agric. Food Chem. (2011) 59: 9120-9126). What are needed are effective methods for improving the bioavailability of curcumin and other therapeutic nutritional compositions and/or pharmaceutical compositions for which bioavailability is a limiting factor.